AUSR_ASPCI
ID AUSR_ASPCI Reviewed; 500 AA.
AC A0A0U5CJT8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Cytochrome P450 monooxygenase ausR {ECO:0000303|PubMed:28233494};
DE EC=1.-.-.- {ECO:0000269|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein R {ECO:0000303|PubMed:28233494};
GN Name=ausR {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14360;
OS Aspergillus calidoustus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=454130;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SF006504;
RX PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT "Draft genome sequences of fungus Aspergillus calidoustus.";
RL Genome Announc. 4:0-0(2016).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=28233494; DOI=10.1021/acschembio.7b00003;
RA Valiante V., Mattern D.J., Schueffler A., Horn F., Walther G.,
RA Scherlach K., Petzke L., Dickhaut J., Guthke R., Hertweck C., Nett M.,
RA Thines E., Brakhage A.A.;
RT "Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus
RT calidoustus.";
RL ACS Chem. Biol. 12:1227-1234(2017).
RN [3]
RP FUNCTION.
RX PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL ACS Chem. Biol. 12:2927-2933(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of calidodehydroaustin, a fungal
CC meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the
CC pathway is the synthesis of 3,5-dimethylorsellinic acid by the
CC polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid
CC is then prenylated by the polyprenyl transferase ausN
CC (PubMed:28233494). Further epoxidation by the FAD-dependent
CC monooxygenase ausM and cyclization by the probable terpene cyclase ausL
CC lead to the formation of protoaustinoid A (By similarity).
CC Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by
CC the combined action of the FAD-binding monooxygenases ausB and ausC,
CC and the dioxygenase ausE (By similarity). Acid-catalyzed keto-
CC rearrangement and ring contraction of the tetraketide portion of
CC preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By
CC similarity). The aldo-keto reductase ausK, with the help of ausH, is
CC involved in the next step by transforming preaustinoid A4 into
CC isoaustinone which is in turn hydroxylated by the P450 monooxygenase
CC ausI to form austinolide (By similarity). The cytochrome P450
CC monooxygenase ausG modifies austinolide to austinol (By similarity).
CC Austinol is further acetylated to austin by the O-acetyltransferase
CC ausP, which spontaneously changes to dehydroaustin (PubMed:28233494).
CC The cytochrome P450 monooxygenase ausR then converts dehydroaustin is
CC into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation
CC catalyzed by ausR permits the O-acetyltransferase ausQ to add an
CC additional acetyl group to the molecule, leading to the formation of
CC acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase
CC ausT catalyzes the reduction of the double bond present between carbon
CC atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-
CC hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an
CC acetylation reaction but also the addition of the PKS ausV diketide
CC product to 1,2-dihydro-7-hydroxydehydroaustin, forming
CC precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-
CC ketoglutarate-dependent dioxygenase converts precalidodehydroaustin
CC into calidodehydroaustin (PubMed:28233494).
CC {ECO:0000250|UniProtKB:Q5AR29, ECO:0000269|PubMed:28233494,
CC ECO:0000269|PubMed:29076725}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28233494}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Eesults in loss of 7-hydroxydehydroaustin and
CC accumulates a new product, 1,2-dihydro-dehydroaustin.
CC {ECO:0000269|PubMed:28233494}.
CC -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC are split in their respective genomes. Genetic rearrangements provoked
CC variability among the clusters and E.nidulans produces the least number
CC of austionoid derivatives with the end products austinol and
CC dehydroaustinol, while P.brasilianum can produce until
CC acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC identified derivatives. {ECO:0000305|PubMed:29076725}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CDMC01000024; CEL11257.1; -; Genomic_DNA.
DR EnsemblFungi; CEL11257; CEL11257; ASPCAL14360.
DR OrthoDB; 572303at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="Cytochrome P450 monooxygenase ausR"
FT /id="PRO_0000453842"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 439
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 500 AA; 56502 MW; C092DE80EE55DC66 CRC64;
MLRLMHPFSA QPNEGVGLYI LWTVAVLFVI FKLLAPAKCD LPTVNGRRRF EIGQYQARRR
FALDGRGIIL NGLRKARAFR VVSQKGPKII LGPEFADEVK SHPACNADVF IAKEFHAHVS
GFEVLRPQQV MKDAIRLKLT RSIGVLMKPM SAETALILET QWGNSDCWHE LDLKSTIASL
VSRVSAVMFV GEELGRDQKW LSIVTNYSSD MFVADLDLCK WPEALRPIAT YFLSSCGKLR
RHIREAALML DPILSERYSA PHNKHNFLDW FEEVAGGRKY NPVLAQLSLA AAAIDTTSDL
IIQTLTDICR FRDSGKLQQD LREEMVRVLR ADGWEKSAMY NLKLLDSVLK ETQRVKPVVV
FGMGRYVTEQ MTLHDGTVIP QGETINVVNT RVWDSAVYPN PLEWDPYRFV RRRDSGDHAA
HLVSPTPDHM GFGLGKHSCP GRFFAATKIK ILLCHILLKY DVKISDEASS TVVSSGNFLF
PDATLSFCVR RRQDNLTIWG
